Phase II IMvigor 210 data shows atezolizumab may prevent progression of metastatic urothelial bladder cancer

Sep 29 2015

Data shows potential for first new treatment modality in over 30 years

Data presented today at the 2015 European Cancer Congress (ECC) demonstrates that the investigational immunotherapy atezolizumab may prevent progression of metastatic urothelial bladder cancer (mUBC) in all age groups by 2.1 months. This Phase II open-label study (IMvigor 210) in mUBC is the first trial of its kind to show that inhibiting PD-L1 in metastatic bladder cancer increases the activity of the immune system which prevents disease progression and may improve survival. Treatment with atezolizumab was shown to shrink tumours which expressed a high level of PD-L1 and a higher overall survival was also observed, however this data has not yet matured.

Bladder cancer is the seventh most common cancer in the UK, and the fourth most common cancer in men with 10,000 people diagnosed in the UK each year. These trends are observed worldwide with around 430,000 new cases diagnosed in 2012 making bladder the ninth most common cancer worldwide. It results in approximately 165,000 deaths globally each year. There have been no major advancements in the treatment of mUBC in nearly 30 years.

Professor Thomas Powles of Barts Cancer Institute commented:

Atezolizumab has shown highly encouraging efficacy in advanced bladder cancer in this phase II study. It is well tolerated and associated with durable responses, which is great news for patients in whom most alternative treatments have limited effectiveness.

Atezolizumab was shown to shrink tumour size in 27% of mUBC patients with high PD-L1 expression, who had previously received platinum chemotherapy in the recent phase II IMvigor 210 study. Through immunohistochemistry testing (IHC), researchers were able to identify individuals with a medium or high expression of PD-L1 on inflitrating immune cells and who appear to be most likely to experience improvement in overall survival, progression free survival and overall response rate. Conversely this also enabled researchers to identify those who were unlikely to benefit versus standard of care due to low PD-L1 expression.

IMvigor 210, an international study involving 316 patients from 17 international centres including Barts Cancer Institute, Queen Mary University of London, met its primary endpoints and demonstrated a safety profile for atezolizumab consistent with that observed in the Phase Ib study, PCD4989g and other atezolizumab monotherapy trials.

There were no unexpected toxicities experienced with atezolizumab. It was generally well-tolerated and adverse events were consistent with what has been reported for atezolizumab in non-small cell lung cancer (NSCLC).

The IMvigor 210 study results follow the Phase 1b trial data presented at the 51st annual meeting of the American Society of Clinical Oncology (ASCO), which showed that atezolizumab shrank tumours (objective response rate; ORR) in 50% of people whose mUBC expressed high levels (IC2/3) of PD-L1 (programmed death ligand-1).

Atezolizumab has received Breakthrough Therapy Designation from the Food and Drug Administration (FDA) – an initiative designed to accelerate the development and review of medicines intended to treat serious diseases and drive patient access.

Atezolizumab has shown potential in other areas of unmet need including non-small cell lung cancer (NSCLC) in the POPLAR and BIRCH phase II studies. The results of both studies are also being presented at ECC and demonstrate clear clinical activity of atezolizumab in PD-L1 selected patient populations.

The European regulatory filings for atezolizumab in these indications are still at an early stage as the pivotal trials are currently ongoing. Once further data is available, Roche will liaise with the appropriate health authorities to ensure that patients and doctors receive this therapeutic option as soon as possible.